过度激活的Rho/ROCK通路介导的心肌缺血再灌注损伤及贝那普利的改善作用

Participation Mechanism of Excessively Activated Rho/ROCK Signaling Pathway in Cardiac Reperfusion Injury and Improvement Effect of Benazepril

目的该研究探索过度激活的Rho/ROCK信号通路在缺血再灌注损伤中的参与机制及贝那普利的改善作用。方法 SD大鼠随机分为4组:假手术组、缺血再灌注组、Y27632组和贝那普利组。采用大鼠冠状动脉左前降支结扎法复制心肌缺血再灌注模型,Y27632组和贝那普利组分别给予对应药物灌胃治疗。分析各组血清中MDA、SOD、GSHpx、Rho/ROCK、MMP2/9及Bax/Bcl2和Caspase3/9的表达。结果模型组血清MDA水平明显增高(15.6→24.1μg/mL)而SOD(83.1→34.6 U/mL)水平明显降低,Rho/ROCK(0.18→0.64;0.19→0.69;0.16→0.65)、MMP2/9(0.28→0.60;0.27→0.63)、Caspase9表达明显增强(0.25→0.68)。Y27632和贝那普利组大鼠的上述异常得到显著的改善。结论贝那普利通过抑制过度激活的Rho/ROCK、激活的细胞凋亡信号通路、改善细胞外基质降解与重构发挥保护缺血再灌注大鼠心肌损伤的作用。

Objective To study the participation mechanism of excessively activated Rho/ROCK signaling pathway in car- diac reperfusion injury and improvement effect of benazepril. Methods The SD rats were randomly divided into 4 groups, namely sham operation group, ischemic reperfusion group, Y27632 group and benazepril group, the cardiac reperfusion in- jury model was copied by ligating the left anterior descending coronary arlery in rats, the Y27632 group and benazepril group were respectively treated with corresponding drug gavage, the expressions of MDA, SOD, GSHpx, Rho/ROCK, MMP2/ 9, Bax/Bel2 and Caspase3/9 in serum of all groups were analyzed. Results The serum NDA level in the model group obvi- ously increased （15.6→24.1 μg/mL）, but the SOD （83,1→34.6 U/mL） level obviously decreased, the expressions of Rho/ROCK （0.18→0.64;0.19→0.69;0.16→0.65）, MMP2/9 （0.28→0.60;0.27→0.63） and Caspase9 were obviously enhanced （0.25→0.68）, the above abnormalities in the Y27632 group and benazepril group were obviously improved. Conclusion Benazepril plays a protection role in rats with cardiac reperfusion injury by suppressing the excessively activated Rho/ROCK, activated cell apoptosis signaling pathway and improving extraeellular matrix degradation and reconstruction.